L-DOPA, administered in "high" doses, produces bizarre alterations in human and in animal behaviors. Reported side effects of L-DOPA therapy include: insomnia, depression, hypomania and paranoid reactions. Alterations in animal behavior include psychomotor excitement, aggresion, sterotyped behavior and hypersexuality. The aim of this reseach will be to more clearly define the neurochemical mechanism of these behavioral changes induced by excessive brain DOPA concentrations, in an attempt to understand the behavioral side effects of L-DOPA therapy in human disease. L-DOPA produces increased dopamine levels in the brain but it also may acutely release serotonin and then inhibit its synthesis. Many of the behavioral alterations produced by DOPA may be due to function of metabolic alteration in serotonergic neurons, and the main emphasis of the proposed research will be to study this relationship. Drugs which block serotonergic receptors (Methysergid, 2-bromo-LSD, and cyproheptadine) or deplete serotonin (p-CPA) will be used as pharmacological tools to study the role of serotonin in the effects of L-DOPA. Reduction of certain L-DOPA behavioral effects by these compounds would indicate indirect (non-dopamine) mediated behavior. (Locomotor activity depression acutely and enhancement when 5-HT is depleted). Behavioral analyses would be complemented by biochemical analyses of L-DOPA's influence on serotonin, dopamine and norepinephrine turnover rates and concentrations in specific brain areas.